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Background: Smokeless tobacco (SLT) is a tobacco-based product consumed without burning or smoking. Snuff, commonly known as naswar, is a widely used SLT product in Pakistan. This study is designed to investigate the concentrations of lead (Pb) and cadmium (Cd) in snuff and their associated health risks to consumers., Methods: Blood samples from snuff consumers and non-consumers were analyzed for Pb and Cd concentrations. Additionally, samples of drinking water and wheat flour were also analyzed for Pb and Cd. Health risk assessments were calculated using hazard quotient (HQ) and incremental lifetime cancer risk (ILCR) for Pb and Cd., Results: Snuff consumers had significantly higher blood-Pb and blood-Cd levels compared to non-consumers. Approximately 38.5 % of snuff consumers were found to exceed blood-Pb levels from the safe limits (10 µg dL⁻¹) of the World Health Organization (WHO), while 48.9 % of snuff consumers were found to exceed blood-Cd levels from the WHO safe range of 0.03-0.12 µg dL⁻¹. Snuff samples contained Pb and Cd concentrations ranging from 5.3 to 22.4 µg g⁻¹ and 0.5-2.2 µg g⁻¹, respectively. Drinking water and wheat flour samples were found within the safe limits for Pb and Cd concentration, suggesting snuff as the primary source of exposure. Health risk assessments indicated elevated HQ values, for Pb (38.9 %) and Cd (14.3 %) detected in snuff, surpassing the safe HQ threshold of 1. Concerning ILCR from snuff, values for Pb were within the acceptable range, but alarmingly 100 % of samples for Cd exceeded the safe limits of USEPA (1.0×10⁻⁴), indicating a significant cancer risk in snuff users., Conclusion: This study highlights the exceeded Pb and Cd concentrations in snuff as well as also reporting significant carcinogenic and non-carcinogenic health risks to consumers. These findings emphasized the urgent need for regulatory bodies to ensure the safety of snuff before selling in the market. Public Health Professionals should also initiate educational campaigns to raise awareness among consumers and manufacturers about various health risks associated with the snuff., Competing Interests: Declaration of Competing Interest I, being the Corresponding author, declared that there is no conflict of interest among the authors. I clearly disclosed no relationship with such a people and organization that could inappropriately influence our submitted work., (Copyright © 2024. Published by Elsevier GmbH.)

Background: There is a well-established link between the use of smokeless tobacco (ST) and the development of oral cancer. This study was conducted to evaluate the impact of tobacco use, quid use, and other adverse habits related to smoking and alcohol consumption on ST-induced localized lesions., Objectives: The aim of the study was to examine the demographic data, frequency and contact duration of ST on the lesion, as well as to conduct a clinical evaluation of these parameters., Material and Methods: A total of 13,442 patients who had been experiencing oral and dental symptoms for a period of at least 6 months were screened. Of these, 334 patients were diagnosed with STor quid-induced localized lesions and had a positive history of ST or quid use. A structured questionnaire was employed to conduct interviews with participants regarding their use of ST and other adverse habits, including smoking and alcohol consumption. Other information related to the use of ST or quid and clinical findings were also recorded, along with the patients' demographic details. A statistical analysis was carried out using the χ2 test and the regression analysis., Results: The overall prevalence of ST-induced localized lesions was found to be 2.48%. In the study population, the majority of participants (58.7%) reported a habit of using khaini, while 26.8% reported using gutkha. The study found significant differences in the severity of ST-induced localized lesions and contact duration, frequency of the habit, and the presence of additional habits such as smoking and/or alcohol consumption. Based on this study, we proposed a modified Greer and Poulson's classification of ST-induced lesions, dividing them into 4 clinical types., Conclusions: Smokeless tobacco-induced localized lesions frequently remain asymptomatic, with patients unaware of their presence. Other adverse habits, including smoking and alcohol consumption, as well as increased ST contact duration were associated with the development of more severe ST-induced localized lesions.

The identification of volatile organic components in snuff was accomplished using GC-MS analysis in this study. The findings of the GC-MS analysis revealed the presence of nicotine, its derivatives, and several other toxic chemicals that are hazardous to human health. Furthermore, the content of 34 elements in four brands of snuff consumed in Neyshabur City was determined by ICP-OES analysis (with five repetitions). The health hazards of measured heavy elements were examined from two perspectives: carcinogenic (7 heavy elements were checked) and non-carcinogenic (4 heavy elements were checked). The investigation of non-carcinogenic hazards from inhalation was based on the computation of the hazard quotient (HQ) factor, and the results indicated that inhaling five heavy metals, Cu, Pb, Ni, Zn, and Cd, does not represent a substantial health risk ((HQ < 1). In contrast, the computed HQ factors for Cr and As were relatively high (1 < HQ < 10), indicating a substantial health risk from breathing these two elements. The carcinogenic factor (CR value) results revealed that the degree of carcinogenic risk for Cd was very low (CR value less than 1 × 10 -6 ) and did not pose a concern to the consumer population. However, the risk of As, Cr, and Ni exposure is considerable in the carcinogenic risk range (CR values between 1 × 10 -6 and 1 × 10 -4 )., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Despite a high (48%) prevalence of snuff use among women with HIV in South Africa, little is known of the attitudes and behaviors of use, strategies for cessation, and potential health risks., Methods: In a cross-sectional study, a questionnaire was administered to adults (≥18 years) with (HIV+) and without HIV (HIV-) who self-reported current snuff use to collect information on demographics, snuff use and cessation attempts, preferred strategies for cessation, other substance use, history of respiratory illness, and mental health., Results: 150 (74 HIV+, 76 HIV-) participants were enrolled; 115 (77%) were daily snuff users, 6 (4%) were current smokers, and 17 (11%) former smokers. Top reasons for current snuff use included improving health (n = 48, 32%), reducing stress (n = 26, 16%), and "being a habit" (n = 38, 25%). Participants believed snuff use to have mostly positive (n = 68, 46%) or no (n = 54, 36%) health impacts, and 57 (38%) participants believed snuff cures headaches. 103 (69%) participants reported a previous quit attempt, and 110 (73%) indicated high interest in quitting snuff. Although 105 (70%) participants indicated that advice from a healthcare provider would aid them in quitting snuff, only 30 (20%) reported ever receiving that advice. A majority of participants (n = 141, 94%) suffer from moderate to high levels of perceived stress, and overall few differences were seen by HIV status., Conclusions: Education on negative impacts of snuff, advice to quit from healthcare providers, and nicotine replacement therapy should be considered in the development of a snuff cessation program., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Clear evidence of an increased risk for SARS-CoV-2 infection among smokers has not been established. We aimed to investigate associations between cigarette smoking or use of snus (snuff) and other nicotine-containing products and a positive SARS-CoV-2 test, taking test behavior into account., Methods: Current tobacco use and testing behavior during the pandemic were recorded by adult participants from the Norwegian Mother, Father and Child Cohort Study and The Norwegian Influenza Pregnancy Cohort. SARS-CoV-2 infection status was obtained from The Norwegian Surveillance System for Communicable Diseases (MSIS) in May 2021 (n = 78,860) and antibody measurements (n = 5581). We used logistic regression models stratified by gender and adjusted for age, education, region, number of household members, and work situation., Results: Snus use was more common among men (26%) than women (9%) and more prevalent than cigarette smoking. We found no clear associations between cigarette smoking or snus and a COVID-19 diagnosis among men. Associations among women were conflicting, indicating that cigarette smoke was negatively associated with a diagnosis (OR 0.51, 95% CI 0.35, 0.75), while no association was found for snus use (OR 1.07, 95% CI 0.86, 1.34). Compared with non-users of tobacco, both cigarette smokers and snus users had increased odds of being tested for SARS-CoV-2., Conclusions: Cigarette smoking, but not snus use, was negatively associated with SARS-CoV-2 infection in women. The lack of an association between snus use and SARS-CoV-2 infection in this population with prevalent snus use does not support the hypothesis of a protective effect of nicotine., (© 2023. The Author(s).)

Introduction: It is unclear whether tobacco in early pregnancy and alcohol use preceding pregnancy are associated with spontaneous abortion. The purpose was to investigate if use of tobacco and/or alcohol is associated with spontaneous abortion among women attending antenatal care, and if age and body mass index (BMI) attenuate the risk., Material and Methods: A population-based cohort study based on data from the Swedish Pregnancy Register. All pregnant women having had the first antenatal visit from January 2014 to July 2018 were included (n = 525 604). The register had information about smoking and use of snuff before and in early pregnancy, as well as data on alcohol habits before pregnancy, measured by the Alcohol Use Disorders Identification Test (AUDIT), a validated questionnaire. Logistic regression analysis was used to estimate the association between lifestyle factors and spontaneous abortion, and multiple imputation was used to impute missing data., Results: In total, 34 867 (6.6%) pregnancies ended in a spontaneous abortion after the first visit to maternal health care. At the first maternal healthcare visit, daily smoking was reported by 24 214 (5.1%), and 6403 (1.2%) used snuff. For 19 837 (4.2%) women, a high alcohol score was reported for the year preceding pregnancy. After adjusting for potential confounders and multiple imputation, use of tobacco was associated with spontaneous abortion; smoking 1-9 cigarettes/day (adjusted odds ratio [aOR] 1.11, 95% confidence interval [CI] 1.04-1.18), smoking 10 or more cigarettes/day (aOR 1.12, 95% CI 1.-1.26), and use of snuff (aOR 1.20, 95% CI 1.06-1.37). Higher AUDIT scores were not significantly associated with spontaneous abortion (AUDIT 6-9: aOR 1.03, 95% CI 0.97-1.10 and AUDIT 10 or more: aOR 1.07, 95% CI 0.94-1.22). Increasing maternal age showed the highest risk of spontaneous abortion from the age of 35, and BMI of 30 kg/m 2 or more increased the risk. There were interactions between different lifestyle factors associated with spontaneous abortion that could either increase or decrease the risk of spontaneous abortion., Conclusions: Smoking and use of snuff were associated with an increased risk of spontaneous abortion. The AUDIT scores preceding pregnancy were not associated with an increased risk of spontaneous abortion, which contradicts the results from previous studies., (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Oral squamous cell carcinoma (OSCC) may arise from premalignant oral lesions (PMOL) in most cases. Minichromosome maintenance 3 (MCM3) is a proliferative marker that has been investigated as a potential diagnostic biomarker in the diagnosis of oral cancer., Objectives: To evaluate the association of MCM3 expression, its clinicopathologic parameters and to identify snuff (also called naswar) as a potential risk factor for changes in MCM3 expression in PMOL and OSCC., Methodology: Immunohistochemistry (IHC) of MCM3 was performed on 32 PMOL, 32 OSCC and 16 normal controls after optimization of IHC methodology. Histoscore (0-300) was used as a scoring system and seven different cut-offs were identified for analyses. Data were analyzed using various statistical tests., Results: Among the seven cutoffs, 40% strong positive cells were found to be a better cut-off as they were associated with many pathological variables (Broder's grade, Aneroth's grade, and mitotic activity). The differential MCM3 expression in oral lesions (PMOL and OSCC) was statistically significant ( p = 0.03). Moreover, MCM3 expression is raised with increased duration and frequency of snuff use., Conclusion: High MCM3 expression is associated with disease progression and is a potential indicator of malignant transformations from PMOL to OSCC. Moreover, the use of snuff is associated with MCM3 over-expression.

Background: Smoke-free tobacco via moist oral snuff (snus) is used daily in more than 20% of Swedish men. Negative effects of cigarette smoking on sperm parameters are well documented, unlike for snuff, despite relevance also for other smoke-free nicotine products., Objectives: We wanted to investigate whether reproductive parameters differed between users and non-users of snuff, and whether the amount of snuff and nicotine exposure mattered., Materials and Methods: Men (n = 613) from the general population, recruited 2000-2010, were physically examined, answered questions on smoking and snuff use, and delivered urine, blood and semen samples. Sperm concentration, total sperm count, semen volume, percent morphologically normal and progressively motile sperm, and DNA fragmentation index (by the Sperm Chromatin Structure Assay) and reproductive hormones were analysed. Nicotine exposure was measured through urinary levels of cotinine. We used general linear models, with adjustments including cigarette smoking, and for semen parameters also abstinence time., Results: After adjustments, total sperm count was 24% lower (P = 0.03) and testosterone 14% higher (P < 0.001) in 109 users of snuff than in non-users, whereas cotinine was positively associated with testosterone and oestradiol (P < 0.001). Numbers of boxes of snuff used per week were associated with testosterone and FSH (P < 0.001)., Discussion: Applied to the general population, the consumption of smoke-free tobacco by the use of snuff was associated with a lower sperm count and a higher testosterone, for which the extent seemed to play a role., Conclusions: Independent of smoking, consumption of snuff was associated with lower total sperm count and different hormone levels. Applying these results to a reported association between sperm count and the chance of pregnancy, men who used snuff would have about a 10% lower chance of fathering a child., (© 2022 American Society of Andrology and European Academy of Andrology.)

Introduction: The objective was to systematically review studies on health outcomes from smokeless tobacco (SLT) products., Methods: We analysed published literature on the health outcomes from SLT use between 01/01/2015 to 01/02/2020, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol using PubMed, Embase, Scopus, and Google Scholar., Results: Of 53 studies included, six were global, 32 from Asia, Middle East and Africa (AMEA), nine from USA and six from Europe. 'Poor'-rated studies predominated (23;43%), in particular, for global (4;66%) and AMEA (16;50%). Health outcomes differed between SLT-products and regions; those in AMEA were associated with higher mortality (overall, cancer, Coronary heart disease (CHD), respiratory but not cardiovascular disease (CVD)), and morbidity (CVD, oral and head and neck cancers), with odds ratios up to 38.7. European studies showed no excess mortality (overall, CVD, from cancers) or morbidity (ischemic heart disease (IHD), stroke, oral, head and neck, pancreatic or colon cancers) from several meta-analyses; single studies reported elevated risk of rectal cancer and respiratory disorders. Pooled study data showed protection against developing Parkinson's disease. US studies showed mixed results for mortality (raised overall, CHD, cancer and smoking-related cancer mortality; no excess risk of respiratory or CVD mortality). Morbidity outcomes were also mixed, with some evidence of increased IHD, stroke and cancer risk (oral, head and neck). No studies reported on switching from cigarettes to SLT-products., Conclusion: Our review demonstrates stark differences between different SLT-products in different regions, ranging from zero harm from European snus to greatly increased health risks in AMEA. The literature on the safety profile for SLT-products for harm reduction is incomplete and potentially misinforming policy and regulation., (© 2021. The Author(s).)

The elite sport environment is one where athletes strive to find a competitive edge, through improved recovery modalities, cognitive performance or physical capacity. Due to this, non-scientifically evidenced and/or pseudo-scientific alternative remedies are ever popular. Snus (an oral tobacco based product containing the highly addictive compound nicotine) is one alternative 'physical and psychological performance enhancer', purported to act as a 'mental and physical booster', 'relaxative' and even as an 'appetite suppressor'. Despite snus having serious adverse health effects, along with no proven benefit to physical or mental performance, observations by the authors working in professional sport, along with several reports in the mainstream media, would suggest that the use of snus in elite sport appears to be increasing. Perhaps most worrying, the use of snus has been reported to be prevalent within younger athletes. It is crucial that athletes are fully educated with regards to the health implications of snus and other oral tobacco-based products, whilst practitioners should be aware of its growing prevalence in sport with strategies in place to discourage its use.

Background: The influence of daily life exposure on the gastrointestinal tract is not fully understood. This study aimed to examine associations between functional gastrointestinal symptoms and sociodemographic status and lifestyle habits in the general population. Methods: The Malmö Offspring Study (MOS) included 2,648 participants from the general population who had answered a questionnaire about sociodemographic status, lifestyle habits, medical health, and self-reported irritable bowel syndrome (IBS). The visual analog scale for IBS (VAS-IBS) was completed to assess gastrointestinal symptoms the past 2 weeks. Subjects with organic gastrointestinal diseases were excluded. Presence of self-reported IBS and gastrointestinal symptoms the past 2 weeks were used as dependent variables to study the associations with age, sex, body mass index, education, occupation, marital status, smoking, snuff using, alcohol drinking frequency, alcohol amount per drinking occasion, physical activity at work, and physical activity during leisure time, using logistic regression and generalized linear model. Results: Self-reported IBS was associated with gastrointestinal symptoms the past 2 weeks ( p < 0.001). There was an association between IBS and female sex ( p < 0.001), former smoking ( p < 0.001), present smoking ( p < 0.001), and an inverse association with drinking 3-4 standard glasses per occasion ( p = 0.038). Gastrointestinal symptoms were associated with age 50-59 years ( p = 0.009), ≥60 years ( p = 0.004), female sex ( p < 0.001), studying ( p = 0.036), unemployment ( p = 0.009), former smoking ( p = 0.001), and present smoking ( p = 0.012). In men, IBS was associated with middle-age and both IBS and gastrointestinal symptoms were associated with unemployment ( p < 0.001 and p = 0.001, respectively). In women, IBS was associated with present smoking ( p = 0.022), and gastrointestinal symptoms were associated with former smoking and inversely associated with higher age ( p = 0.006) and intermediate physical activity at work ( p = 0.008). No associations were found with BMI, education, marital status, or snuff using. Conclusion: Self-reported IBS in the general population shows strongest association with female sex and smoking, whereas gastrointestinal symptoms also are associated with unemployment and inversely associated with higher age. In men, both IBS and gastrointestinal symptoms are associated with unemployment. In women, both IBS and gastrointestinal symptoms are associated with smoking, whereas symptoms are inversely associated with higher age and intermediate physical activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nilsson and Ohlsson.)

Background: Cigarette smoking is a well-known risk factor for cardiovascular disease (CVD), but whether smokeless tobacco such as snuff is associated with the risk of CVD is still unclear. We investigated the association of the use of Swedish oral moist snuff (snus) with a broad range of CVDs and CVD mortality., Methods: We used data from a population-based cohort of 41,162 Swedish adults with a mean baseline age of 70 (56-94) years who completed questionnaires regarding snus use and other lifestyle habits and health characteristics. Participants were followed up for incident cardiovascular outcomes and death over 8 years through linkage to the Swedish National Patient and Death Registers. Hazard ratios (HR) were estimated by Cox proportional hazards regression. We conducted analyses among all subjects as well as among never smokers to reduce residual confounding from smoking., Results: After adjustment for smoking and other confounders, snus use was not associated with myocardial infarction, heart failure, atrial fibrillation, aortic valve stenosis, abdominal aortic aneurysm, stroke, or CVD mortality. However, in never smokers, snus use was associated with a statistically significant increased risk of total and ischemic stroke (HRs [95% confidence intervals] = 1.52 [1.01-2.30] and 1.63 [1.05-2.54], respectively) and non-significantly positively associated with some other CVDs., Conclusions: In this middle-aged and elderly Swedish population, current Swedish snus use was not associated with the risk of major heart and valvular diseases, abdominal aortic aneurysm, or CVD mortality in the entire study population, but was linked to an increased risk of stroke in never smokers.

Background and Aim: Smoking rates are decreasing in Norway while the use of snus has increased. We aimed to investigate the co-occurrence of, and the socio-demographics, personality and substance use characteristics associated with, student smoking and snus use., Methods: Survey data were collected among students in higher education in Bergen, Norway in 2015 ( N = 11,236, response rate 39.4%). Multinomial regression analyses comparing snus users and smokers to non-users and non-smokers, respectively, on demographic, personality and substance use variables were conducted. Regression analyses comparing current dual users to current smokers and current snus users and comparing daily smokers to daily snus users, on demographic, personality and substance use variables were also conducted., Results: In total 67.9% of ever snus users identified themselves as non-smokers (past and current). Several demographic, personality and substance use characteristics associated with smoking and snus use were identified (all = p < . 05), some of which were common for both (e.g., use of cannabis) and some which were exclusively associated with either smoking (e.g., neuroticism) or snus use (e.g., extroversion)., Conclusion: The current study contributes with several novel findings regarding traits associated with smoking and snus use. Though limited by a cross-sectional design, the current findings may suggest that the group of students using snus consists of a combination of previous smokers, students who would have smoked if snus was not available and a new segment who may not have used nicotine if snus was not available., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

The objective of this study was to assess the association between tobacco/nicotine use and type and intensity of sport. Data were drawn from the second follow-up of the Cohort Study on Substance Use Risk Factors. Young Swiss men completed a questionnaire about tobacco/nicotine use (cigarette, vaping, snus, snuff), type and intensity of sport and other demographic and medical variables. Among the 5414 included participants (mean age 25.5), 3434 (63.4%) reported regularly practicing a sport. They had a lower rate of cigarette smoking (32.3%) compared with participants not practicing a sport (44.6%) but a higher rate of snus use (15.0% vs. 10.0%). In adjusted models, individual-sport participants were less likely to use snus and snuff (OR = 0.63, 95% CI = 0.51-0.77 and OR = 0.73, 95% CI = 0.61-0.88), compared with team-sport participants. The association was inversed for vaping users (OR = 1.54, 95% CI = 1.03-2.30). Furthermore, participants who practiced high-intensity sports had a lower likelihood to smoke cigarettes (OR = 0.63, 95% CI = 0.52-0.78) compared with low-intensity sports. Our findings suggest that type and intensity of sport are associated with tobacco/nicotine use. Youth who practice an individual sport are less likely to use snus or snuff and more likely to vape compared with a team sport. This could help better target smoking prevention in young people.

Background: Several studies have investigated the role of snus as an aid to become smoke-free, but few have focused on who use snus, how they perceive snus use, why and how they quit, and their perception of being non-snus users. The purpose of this paper is to describe snus cessation patterns., Methods: Respondents are part of a 7-year follow-up of former smokers in Sweden. Initially, 1400 respondents were contacted regarding participation and 705 answered a web-based survey (response rate 50%). Out of them, 118 had used snus. The analyses include percentage distributions, as well as factor analyses of inventories, and configural frequency analysis in order to examine configurations of snus-related patterns., Results: Over 80% found snus of great importance to succeed with smoking cessation and half of them continued to use snus on a long term. Those who experienced both physical and psychological effects of switching to snus were the ones who continued and vice versa; those who did not experience such effects quit using snus. None made use of professional help but had their own strategies (60%), and most respondents who quit obtained psychological benefits (68%)., Conclusions: The distinction between the concepts smoke-free, tobacco-free, and nicotine-free contributes to nuances in the debate on snus as harm reduction. Continued snus use does not mean that snus is not an effective aid to become smoke-free. Snus cessation is mostly mentioned in relation to advices on how to succeed, but the cessation process has rarely been described; therefore, this study expands the knowledge on this quite neglected topic and contributes to a more nuanced picture of snus cessation.

Background: Worldwide, tobacco use has caused over 100 million deaths in the twentieth century and is projected to cause death in up to one billion people in the twenty-first century. It is a leading cause of early death and disability in over 100 countries and accounts for over 11% of global deaths, disproportionately affecting low- and middle-income countries. The purpose of the study was to examine a variety of social determinants of tobacco use in the Democratic Republic of the Congo, including region, sex, ethnicity, education, literacy, wealth index and place of residence, to gain insights with regard to tobacco use among sub-national groups., Methods: This project was a secondary data analysis of the 2013-2014 Demographics and Health Survey (DHS) for the Democratic Republic of the Congo. Logistic regressions predicting smoking, use of snuff and smoking cigars or natural tobacco as dichotomous variables were conducted. Independent variables included age, educational level, religion, rurality, literacy, wealth index, occupation and ethnicity., Results: Tobacco use is highest among those with less education and low literacy. It was also highest among the working poor. Older age and living in larger cities were predictive of smoking, although the relationship between age and smoking was not linear. There was a strong linear effect for wealth. Being in a professional, technical or managerial position was highly protective against smoking while being engaged in services, skilled and unskilled manual labor, and the army had significantly greater odds of smoking., Conclusions: Data indicate that tobacco use in the DRC, as is common in the developing world, is heavily concentrated in the working poor with lower educational status. Higher educational status is consistently predictive of avoiding tobacco use. Additionally, examining only national-level data to ascertain tobacco use levels and patterns may lead to mistaken conclusions that can lead to inefficient and ineffective allocation of resources aimed at controlling tobacco use.

Background/aim/aim: Smokeless tobacco has been associated with oral cavity cancer for several decades. The incidence of oral cavity cancer is higher in some parts of the world especially South and South-East Asia including Pakistan. The aim of current study was to evaluate the risk of oral cavity cancer among smokeless tobacco users in our country., Materials and Methodsand Methods: A case-control study was conducted between November 2016 and September 2017. Patients diagnosed with oral cavity cancer receiving treatment were included as cases and the attendants of various cancer patients visiting the hospital during the study period were included in the study as controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated and all reported P-values were considered significant at < 0.05., Results: The crude OR for the “ever smokeless tobacco users” among cases and controls came out to be 4.98 (95%CI; 2.76–9.01). The OR for snuff users among cases and controls was 4.82 (95%CI; 2.37–9.80) and that for betel leaf users was 4.42 (95%CI; 1.66–11.91) after adjusting for smoking and age., Conclusion: Our study provided strong evidence for snuff and betel leaf to be independent risk factors for oral cavity cancer., Competing Interests: All authors have read the manuscript and agreed with the submission with no conflicts of interest to disclose., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Introduction: This study aimed to assess the association between toombak (smokeless tobacco) advertisement at point-of-sale (PoS) and its use among adolescents in Sudan., Methods: A cross-sectional school-based and self-administered questionnaire study was conducted. Schools were randomly selected using a one-stage stratified sampling procedure, during 2013-2014, as part of a larger research project focusing on the use of toombak among secondary school students in Khartoum State, Sudan. The sample size was 1526 students. Data were collected on exposure to toombak advertisement, social acceptability, perceived accessibility to toombak, susceptibility, and toombak use., Results: A total of 41.8% of the adolescents were exposed to an advertisement at PoS, while 12.5% perceived direct access to toombak, 5.3% reported that they were susceptible to use toombak, and 10.9% were ever toombak users. Exposure to the advertisement of toombak at PoS was found to be associated with the older age group (44.3%) (p≤0.05). Males were more than females (45.2% vs 38.8%; p≤0.05). Those exposed to toombak advertisements at PoS reported more social acceptability towards toombak (48.9% vs 37.6%; p≤0.001) and direct accessibility to toombak (68.8% vs 47.2%; p≤0.05). Ever toombak users reported higher exposure to advertisements than non-users (54.5% vs 40.3%; p≤0.001)., Conclusions: Exposure to toombak advertisements at PoS was found to be high and associated with increased toombak use in Khartoum State, Sudan, in addition to increasing social acceptability to its use and perceived easy accessibility. The current law, which bans toombak advertisement and promotion at PoS, needs to be enforced., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2020 Almahdi H. M.)

Background: The range of risk reduced alternatives to smoking tobacco is increasing and so is use among pregnant women. The substantial harms of smoking during pregnancy are well established and there is reason to believe that nicotine alone is somewhat harmful. Differences in the exposure chemistry strongly suggest that the effects of using smoke-free nicotine products (including pharmaceutical nicotine products, smokeless tobacco, and electronic cigarettes containing nicotine) fall somewhere in the range between zero risk to the risk from smoking. How much lower risk these consumption choices are in terms of pregnancy outcomes, however, remains uncertain., Methods: We reviewed the literature on smoke-free nicotine and tobacco product exposure and birth-outcome endpoints. Studies were included if they compared outcomes to either no nicotine use or smoking. We searched Google Scholar using broad search terms and additional articles were snowballed from citations. We report what could be learned from each study, given its methods., Results: Of the 21 studies reviewed, 12 reported on the use of nicotine replacement therapies, 7 on Swedish snus, 1 on Alaskan iq'mik, and 1 on e-cigarettes. The range of results tends to support the prediction that smoke-free product use during pregnancy probably increases the risk of some negative birth outcomes, but that any effect is less than that from smoking. However, the limitations of epidemiology are such that no more-precise a conclusion is possible., Discussion: The available epidemiology does not change our prior beliefs, based on other evidence and knowledge, that the risks from smoke-free nicotine and tobacco are lower than those for smoking, though it suggests they are non-zero. However, it also demonstrates that the epidemiology is unlikely to provide precise quantitative estimates. This is not just a matter of lack of studies; given the inherent limitation of these studies, doubling or tripling the corpus of available studies would add little precision. For the foreseeable future, decisions about using these products will need to be made based on rough estimates, based on a variety of forms of evidence, and qualitative comparisons.

Globally, smokeless tobacco (ST) includes a wide array of chemically diverse products generally used in the oral cavity. Although ST has been widely investigated, this study was undertaken to determine the levels of sugars (mono- and di-saccharides), alditols, and humectants present in major ST categories/subcategories by using high performance liquid chromatography coupled with a triple quadrupole mass spectrometer (HPLC-MS/MS). The products studied included chewing tobacco (loose leaf, plug, twist), US moist snuff, Swedish snus, creamy snuff, dry snuff, dissolvable tobacco products, and tobacco-coated toothpicks. The highest mean sugar level was detected in chewing tobacco (9.3-27.5%, w/w ), followed by dissolvable tobacco (2.1%); all other products were lower than 1%. Creamy snuff had the highest mean alditol levels (22.6%), followed by dissolvable tobacco (15.4%); all others had levels lower than 1%. The detected mean humectant levels ranged from non-detectable to 5.9%. This study demonstrates the broad chemical diversity among ST. This research may aid researchers and public health advocates investigating the exposures and risks of ST. [Beitr. Tabakforsch. Int. 28 (2019) 203-213].

Background: Incidence of oral tongue squamous cell carcinoma (OTC) is rising among those under age 50 years. The etiology is unknown., Methods: A total of 395 cases of OTC diagnosed and/or treated at Vanderbilt University Medical Center between 2000 and 2017 were identified. Of those, 113 (28.6%) were early onset (age < 50 years). Logistic regression was used to identify factors associated with early onset OTC. Cox proportional hazards models evaluated survival and recurrence., Results: Compared to typical onset patients, patients with early onset OTC were more likely to receive multimodality treatment (surgery and radiation; adjusted odds ratio [aOR], 2.7; 95% confidence interval [CI], 1.2-6.3) and report a history of snuff use (aOR, 5.4; 95% CI, 1.8-15.8) and were less likely to report a history of cigarette use (aOR, 0.5; 95% CI, 0.2-0.9). Early onset patients had better overall survival (adjusted hazard ratio, 0.6)., Conclusions: This is the largest study to evaluate factors associated with early onset OTC and the first to report an association with snuff., (© 2019 Wiley Periodicals, Inc.)

The major components of 70 brands of smokeless tobacco products (STPs) from Sweden and the US were determined to provide greater understanding of the general chemical composition of these products. Various styles of STPs were examined: loose and portion snus from Sweden, and chewing tobacco, dry snuff, moist snuff, hard pellet, soft pellet and plug from the US. The components analysed were major STP components such as water, nicotine, sugars, humectants, sodium ions, chloride ions and ash. The relative quantities of the components varied significantly between different styles of STP. The major component of moist snuff and Swedish loose snus is water. With Swedish portion snus water and pouch material comprise more than half of the product mass; with chewing tobaccos water and sugars comprise around 60% of the products. With these STPs, tobacco was a minor component (30-35%) of the product mass. By way of contrast, tobacco comprised the majority (around 70-90%) of the product mass with dry snuff, hard pellet and soft pellet products. Additives such as sugars, propylene glycol, glycerol, and sodium chloride comprised up to around 12% of the STPs, except for plug and chewing tobaccos where sugars comprised 15-30% by mass of the STP on average. Significant disagreements were found amongst alternative methods of determining water/moisture content for STPs. In particular the oven method, commonly used to determine moisture in tobacco, gave significantly higher values than the Karl Fischer water method when propylene glycol was present. Smaller but similar differences were found using the Near-Infrared method. Choice of measurement technique has important consequences for accuracy of toxicant levels when reporting on a dry-weight basis, a commonly used parameter in smokeless tobacco research and emerging regulatory standards. Conversion to a DWB was also found to produce a preferential bias between and within different STP categories in favour of drier products. These data provide greater understanding of differences in the compositions of contemporary smokeless tobacco products, and demonstrate challenges associated with conversion of actual product contents to dry weight basis values., Competing Interests: The study was funded by British American Tobacco (BAT). At the time of the study KM, HK and AF were paid employees of BAT. AP is a paid consultant to BAT. BR’s research is funded in-part by unrestricted grants from Tobacco Manufacturers (including BAT) to the University of Louisville.

Background: We analyzed in detail the studies utilized in most recent global systematic review of risk of cancer mortality with smokeless tobacco (SLT) use to report challenges in the available data that limit the understanding of association between SLT use and cancer mortality. Methods: For each study, we documented study design, reporting of mortality risk by type of SLT variant, SLT use frequency, and sex of SLT user for oral, oesophageal, pharyngeal, laryngeal and orolaryngeal cancers. These findings are discussed within the context of prevalence of SLT use by geographic regions and sex. Results: Majority of studies reported mortality risk for oral (70.6%) followed by oesophageal cancer (38.2%). The availability of population-based evidence was low (35.3%). The geographic distribution of studies did not reflect the geographic distribution of countries with high SLT consumption; 61.8% of the studies were from India followed by Sweden (20.6%). Hospital-based (84.2%) studies reported risk with chewing tobacco and the population-based studies (61.5%) with non-chewing tobacco. Hardly any study reported on a particular type of SLT. Definition of SLT use as current, ever or former was limited without consideration of the wide variations in frequency and duration of use within these patterns. Mortality risk reporting for males dominated all cancers other than oral (50% males). Conclusions: Unless the methodological and generalizability challenges identified in this review are addressed in future research to develop a stronger scientific basis of the association of SLT use and cancer mortality, we would continue to face significant challenges in monitoring the health effects of SLT., (Creative Commons Attribution License)

Background: Use of smokeless tobacco (ST, moist snuff and chewing tobacco) is elevated among male rural youth, particularly participants in certain sports, including baseball., Objectives: This study aimed to assess factors associated with adolescent male athletes' ST-related behaviors over time, including: baseline use, initiation, and progression in use intensity in a school-based longitudinal cohort., Methods: Baseline and one-year follow-up questionnaires assessed sociodemographic characteristics, environmental factors, and tobacco-related perceptions and behaviors among 9- to12th-grade interscholastic baseball players in 36 rural California schools. Population characteristics were compared among ST use categories (never, experimental, and experienced users). Multivariable models using generalized estimating equations were estimated for outcomes among baseline ST never-users (ST susceptibility and future initiation) and experimenters (ST expectations and progression in ST use)., Results: Of 594 participants, over half (57%) had ever tried a tobacco product and the most common products tried were ST (36%) and electronic cigarettes (36%). Being older, perceiving less ST harm, being Non-Hispanic White, using alcohol or other tobacco products, having family or friends who use ST, and being receptive to advertising were associated with greater baseline ST use. Baseline alcohol consumption, lower perceived ST harm, peer use, and susceptibility and expectations were predictive of ST initiation and/or progression at one-year follow-up. Conclusion/Importance: Certain environmental, socio-demographic, cognitive, and behavioral factors predict ST susceptibility and later initiation and progression in use. Interventions addressing these factors have potential to prevent ST uptake and continued use within this high-risk adolescent population.

Differences in health risks between different styles of smokeless tobacco products (STPs) have prompted interest in their relative levels of toxic chemicals. We report here the development of methods for the analysis of STPs for coumarin and for α-angelica lactone (α-AL), both of which have been included in various published lists of tobacco toxicants. We have also determined the concentrations of these lactones in commercial STPs from the US and Sweden, representing 80-90% of the 2010 market share for all the major STP categories in these two countries: 65 products (plus two reference products) for coumarin and 66 commercial products for α-AL. For coumarin, methanol extracts of the STPs were analysed by HPLC/MS/MS. The lower limit of quantification (LOQ) and limit of detection (LOD) were, respectively, 100 and 30 ng coumarin/g of STP on a wet weight basis (WWB). Alpha-AL was determined via direct headspace GC/MS. The LOQ and LOD were 65 and 30 ng/g WWB respectively. Coumarin was detected In 3/33 Swedish snus, 5/13 US chewing tobaccos, 16/16 moist snuffs and 5/6 dry snuffs. Concentrations in those samples with quantifiable coumarin contents ranged from 186 to 1656 ng/g WWB. Concentrations of coumarin measured in this study were consistent with levels naturally found in tobacco. None of the STPs analysed would significantly contribute to coumarin exposure in consumers compared with dietary sources, and estimated exposure levels were 1000× lower than the European Food Safety Authority Tolerable Daily Intake. Hence the relevance of coumarin to the toxicity of STPs and its inclusion in the FDA's list of harmful and potentially harmful compounds list is questionable. Measurements of α-AL in these STPs found that the majority did not have quantifiable contents, however, for three STPs concentrations of α-AL were above the LOQ (116-140 ng/g WWB) and for four other STPs concentrations of α-AL could be estimated between the LOD and LOQ. Beta-angelica lactone was tentatively identified in three of the STPs but the levels could not be reliably quantified. The levels of α-AL in tobacco products are reported here for the first time, but the relevance of α-AL to the toxicity of STPs is also highly questionable given that it has GRAS status as a permitted food additive.

Introduction: Oral moist snuff is widely used in Sweden including during pregnancy. Maternal snuff use has been associated with increased risks of adverse pregnancy outcomes in epidemiological studies. Self-reported maternal snuff use has not been validated previously. The main objective of this study was to validate self-reported snuff use in pregnancy in a prospective cohort study and in the Medical Birth Register., Material and Methods: A prospective Swedish cohort study, 2005-2011, in which 572 women were asked to participate. Of 474 recruited women, 381 non-smokers (263 snuff users and 118 non-tobacco users) were included in the main analyses. Participants prospectively reported snuff use through questionnaires. Medical Birth Register data on the participants was obtained. Maternal urine cotinine was collected in late pregnancy and was used as a biomarker., Results: Cotinine levels in maternal urine confirmed a high validity of self-reported snuff use through questionnaires in late pregnancy; sensitivity and specificity values were 98% and 96%, respectively. In the Medical Birth Register, 45% of the snuff users were misclassified as nonusers in late pregnancy. There were significant differences in median cotinine levels between users of mini pouches and users of standard pouches, but there was a great difference of cotinine levels among users with similar number of pouches used daily., Conclusions: Self-reported snuff use through questionnaires has high validity. In the Medical Birth Register, in late pregnancy, many snuff users were misclassified as nonusers. As a consequence, there is a risk of underestimating the harmful effects of snuff use when using late pregnancy Medical Birth Register data., (© 2018 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: We are interested in comparing the levels of harmful or potentially harmful constituents in Swedish and American smokeless tobacco products (STPs). We report here the concentrations of the IARC Group 2 A (probable human) carcinogen ethyl carbamate (EC) in seventy commercial STPs from the US and Sweden, representing 80-90% of the market share of the major STP categories in these countries. We also examine the effects of various additives, processing and storage conditions on EC concentrations in experimental snus samples., Results: EC was determined from aqueous extracts of the STPs using ultra performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS). EC was undetectable (< 20 ng/g wet weight basis WWB) in 60% of the commercial STPs, including all the chewing tobacco (CT), dry snuff (DS), hard pellet (HP), soft pellet (SP), and plug products. Measurable levels of EC were found in 11/16 (69%) of the moist snuff (MS) samples (average 154 ng/g in those samples containing EC) and 19/32 (59%) of the Swedish snus samples (average 35 ng/g). For the experimental snus samples, EC was only observed in ethanol treated samples. EC concentrations increased significantly with ethanol concentrations (0-4%) and with storage time (up to 24 weeks) and temperature (8 °C vs 20 °C). EC concentrations were lower at lower pHs but were unaffected by adding nitrogenous precursors identified from food studies (citrulline and urea), increasing water content or by pasteurisation. Added EC was stable in the STP matrix, but evaporative losses were significant when samples were stored for several weeks in open containers at 8 °C., Conclusions: EC was found in measurable amounts only in some moist STPs i.e. pasteurised Swedish snus and unpasteurised US MS; it is not a ubiquitous contaminant of STPs. The presence of ethanol contributed significantly to the presence of EC in experimental snus samples, more significantly at higher pH levels. Sample age also was a key determinant of EC content. In contrast, pasteurisation and fermentation do not appear to directly influence EC levels. Using published consumption rates and mouth level exposures, on average STP consumers are exposed to lower EC levels from STP use than from food consumption.

Aims and Objectives: Nicotine absorption through the mucous membrane is directly proportional to pH, so the snuff is buffered to pH of 8-9 by adding sodium carbonate. The objective of the present study is to assess the impact of various forms of sodium carbonate in snuff on mucosal conditions., Materials and Methods: The present cross-sectional study was conducted on 284 participants. Snuff users adding sodium carbonate were further splitted into two groups, that is, one group using sodium carbonate in premixed form, that is, (already mixed within pouches) and other group adding sodium carbonate separately (freshly mixed). The parametric one-way (ANOVA) of variance, stepwise regression analysis, and multiple logistic regression analysis have been done to narrate the relationship between variables of different forms of sodium carbonate in snuff and different oral conditions., Results: The statistics of our study reveals highly significant relationship between snuff users using sodium carbonate in freshly mixed (0.001**) form than that of premixed form ( P = 0.030*)., Conclusion: The present study narrates that there seems to be liaison between the use of sodium carbonate in snuff and oral mucosal lesions., Competing Interests: There are no conflicts of interest.

There is considerable interest in the chemical composition of smokeless tobacco products (STPs), owing to health concerns associated with their use. Previous studies have documented levels of 210 Po, 210 Pb and uranium in STP samples. Here, the levels of 13 α-particle and 15 β-radiation emitting radionuclides have been measured in a broad and representative range of contemporary STPs commercially available in the United States and Sweden. For each radionuclide, the level of radioactivity and calculated mass per gram of STP are reported. The results indicate that, among 34 Swedish snus and 44 US STPs, a more complex radionuclide content exists than previously reported for these products. Of the 28 radionuclides examined, 13 were detected and quantified in one or more STPs. The most frequently identified radionuclides in these STPs were 40 K, 14 C, 210 Po and 226 Ra. Over half the STPs also contained 228 Th, and an additional 8 radionuclides were identified in a small number of STPs. The presence of 14 C, 3 H and 230 Th are reported in tobacco for the first time. The activity of β-emitters was much greater than those of α-emitters, and the β-emitter 40 K was present in the STPs with both the greatest radioactivity and mass concentrations. Since the three radionuclides included in the FDA's HPHC list were either not detected ( 235 U), identified in only three of 78 samples ( 238 U), and/or had activity levels over fifty times lower than that of 40 K ( 210 Po, 238 U), there may be a rationale for reconsidering the radionuclides currently included in the FDA HPHC list, particularly with respect to 40 K. Using a model of the physical and biological compartments which must be considered to estimate the exposure of STP users to radionuclides, we conclude that exposure from α-emitters may be minimal to STP users, but 40 K in particular may expose the oral cavities of STP users to β-radiation. Although a more comprehensive picture of the radioisotope content of STPs has emerged from this study, epidemiological evidence suggests that the levels of radionuclides measured in this study appear unlikely to present significant risks to STP users.

Smokeless tobacco products contain numerous chemical compounds, including known human carcinogens. Other smokeless tobacco constituents, including bacteria, may also contribute to adverse health effects among smokeless tobacco users. However, there is a lack of data regarding the microbial constituents of smokeless tobacco. Our goal was to characterize the bacterial microbiota of different smokeless tobacco products and evaluate differences across product types and brands. DNA was extracted from 15 brands of smokeless tobacco products (including dry snuff, moist snuff, snus, and Swedish snus) and 6 handmade products (e.g., toombak) using an enzymatic and mechanical lysis approach. Bacterial community profiling was performed using PCR amplification of the V1-V2 hypervariable region of the 16S rRNA gene, followed by 454 pyrosequencing of the resulting amplicons and sequence analysis using the QIIME package. Total viable counts were also determined to estimate the number of viable bacteria present in each product. Average total viable counts ranged from 0 to 9.35 × 10 7  CFU g -1 . Analysis of the 16S rRNA gene sequences revealed high bacterial diversity across the majority of products tested: dry snuff products where characterized by the highest diversity indices compared to other products. The most dominant bacterial phyla across all products were Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes. Significant differences in both bacterial community composition and in silico predicted gene content were observed between smokeless tobacco product types and between brands of specific smokeless tobacco products. These data are useful in order to comprehensively address potential health risks associated with the use of smokeless tobacco products.

Smokeless tobacco (ST) products vary significantly in their oral carcinogenicity. Much is known about the differences in the chemical, but not the bacterial, constituents of these products. In this study, we explored the composition and function of the bacteriome in ST products from four countries using quantitative polymerase chain reaction (qPCR) and 16S rRNA-based next generation sequencing. The bacterial load (16S rRNA copies/gram) was lowest in Swedish snus (3.4 × 10⁶) and highest in Yemeni shammah (6.6 × 10 11 ). A total of 491 species-level taxa, many of which are potentially novel, belonging to 178 genera and 11 phyla were identified. Species richness and diversity were highest for Swedish snus and lowest for Yemeni shammah. Bacillus , Paenibacillus , and Oceanobacillus spp. were the most abundant in American snuff; species of Pseudomonas , Massilia , Propionibacterium , Puniceispirillum , and Gloeothece predominated in Swedish snus. In Sudanese toombak, Facklamia , Desemzia , Atopostipes , and Lysinibacillus spp. accounted for the majority of the bacteriome. Yemeni shammah exclusively contained Bacillus spp. Functional prediction by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) showed that genes encoding cadmium/zinc and nickel transport systems were enriched in the presumptively "high carcinogenicity" products. The bacteriome of ST products thus differed qualitatively, quantitatively, and functionally. The relevance of these differences, particularly with respect to nickel and cadmium, to oral carcinogenesis warrants further investigation.

Objective: Tobacco smoking is a risk factor for gastroesophageal reflux, but whether other tobacco products increase the risk is unclear. The aim of this study was to investigate if snus increases the risk of gastroesophageal reflux symptoms (GERS)., Material and Methods: The study was based on the third Nord-Trøndelag health study (HUNT3), a population-based study of all adult residents in Nord-Trøndelag County, Norway, performed in 2006-2009. The association between self-reported severe heartburn/regurgitation and snus use was assessed by logistic regression., Results: Compared to never snus users, daily snus users had a reduced risk of GERS (OR 0.77, 95% confidence interval [CI] 0.64-0.93), while previous snus users and those using <2 boxes of snus/month had an increased risk (OR 1.20, 95% CI 1.00-1.46 and OR 1.41, 95% CI 1.02-1.96, respectively). There was no association between age when starting using snus and GERS. Snus users who started using snus to quit or cut down on cigarette smoking, who started using both snus and cigarettes or cigarettes alone had an increased risk of GERS. Snus users <30 years of age had an increased risk of GERS (OR 1.49, 95% CI 1.02-2.16), while those aged between 50-60 and 60-70 years had a reduced risk (OR 0.67, 95% CI 0.49-0.93 and OR 0.51, 95% CI 0.28-0.94, respectively)., Conclusions: Daily snus users had a reduced risk of GERS. However, previous snus users and subgroups of snus users had an increased risk of GERS indicating reverse causality, such that snus use could increase the risk of GERS.

Objective: To study the associations of maternal tobacco use (smoking or use of snuff) and risk of extremely preterm birth, and if tobacco cessation before antenatal booking influences this risk. To study the association between tobacco use and spontaneous or medically indicated onset of delivery., Design: Population-based cohort study., Setting: Sweden., Population: All live singleton births, registered in the Swedish Medical Birth Register, 1999-2012., Methods: Odds ratios (OR) with 95% confidence intervals (CI) were calculated using multiple logistic regression analysis., Main Outcome Measures: Extremely preterm birth (<28 weeks of gestation), very preterm birth (28-31 weeks), moderately preterm birth (32-36 weeks)., Results: Maternal snuff use (OR 1.58; 95% CI: 1.14-2.21) and smoking (OR 1.61; 95% CI: 1.39-1.87 and OR 1.91; 95% CI: 1.53-2.39 for moderate and heavy smoking, respectively) were associated with an increased risk of extremely preterm birth. When cessation of tobacco use was obtained there was no increased risk of preterm birth. Snuff use was associated with a twofold risk increase of medically indicated extremely preterm birth, whereas smoking was associated with increased risks of both medically indicated and spontaneous extremely preterm birth., Conclusions: Snuff use and smoking in pregnancy were associated with increased risks of extremely preterm birth. Women who stopped using tobacco before the antenatal booking had no increased risk. These findings indicate that nicotine, the common substance in cigarettes and snuff, is involved in the mechanisms behind preterm birth. The use of nicotine should be minimized in pregnancy., Tweetable Abstract: Tobacco use increases risk of extremely preterm birth. Cessation is preventive. Avoid nicotine in pregnancy., (© 2016 Royal College of Obstetricians and Gynaecologists.)

This study was conceived in an attempt to explain the unexpectedly high frequency of elevated levels of serum cotinine measured retrospectively in a cohort of predominantly black South African females with rheumatoid arthritis (RA), findings that were inconsistent with the smoking histories derived from health questionnaires. The discrepant findings suggested either a greater tendency towards underreporting of smoking status in the study cohort, or possible confounding effects of the use of smokeless tobacco products. In addition to the cohort of RA patients (n = 138, of whom 115 (83 %) were female), blood samples were also taken from a second cohort consisting of 29 declared smokers, 18 (62 %) of whom where females, 29 smokeless tobacco (SLT) users (all female), and 22 non-users of any tobacco products, 18 (82 %) of whom were females. Serum cotinine levels were determined using an ELISA procedure. Cotinine levels of >10.0 ng/ml were detected in serum specimens from 43 (31 %), RA patients of whom 35 (81 %) were female, with a median value of 50.1 ng/ml and interquartile range (iqr) of 68.6. Only 18 of the 35 females indicated that they smoked. The groups of declared smokers and SLT users had equivalent median serum cotinine levels of 88.0 ng/ml (iqr = 10.8 ng/ml) and 87.0 ng/ml (iqr = 15.6 ng/ml), respectively, while cotinine was undetectable in specimens from non-tobacco product users (<0.2 ng/ml). Users of SLT products in South Africa are predominantly female and have serum cotinine levels which are comparable with those of current smokers, raising concerns about the validity of measurement of cotinine as the sole objective marker of smoking status in populations with high usage of SLTs. This situation can be rectified by ensuring that usage of SLT products is accurately recorded in health questionnaires, while inclusion of measurement of one or more additional, objective biomarkers of smoking in combination with cotinine may enable reliable distinction between smoking and usage of SLTs which, given the associated risks, is a strategy of particular relevance in RA.

Tobacco use is strongly associated with cardiovascular disease and the only avoidable risk factor associated with development of aortic aneurysm. While smoking is the most common form of tobacco use, snuff and other oral tobacco products are gaining popularity, but research on potentially toxic effects of oral tobacco use has not kept pace with the increase in its use. Here, we demonstrate that cigarette smoke and snuff extracts are highly toxic to developing zebrafish embryos. Exposure to such extracts led to a palette of toxic effects including early embryonic mortality, developmental delay, cerebral hemorrhages, defects in lymphatics development and ventricular function, and aneurysm development. Both cigarette smoke and snuff were more toxic than pure nicotine, indicating that other compounds in these products are also associated with toxicity. While some toxicities were found following exposure to both types of tobacco product, other toxicities, including developmental delay and aneurysm development, were specifically observed in the snuff extract group, whereas cerebral hemorrhages were only found in the group exposed to cigarette smoke extract. These findings deepen our understanding of the pathogenic effects of cigarette smoking and snuff use on the cardiovascular system and illustrate the benefits of using zebrafish to study mechanisms involved in aneurysm development., (© 2016. Published by The Company of Biologists Ltd.)

Introduction: We assessed US adult smokeless tobacco (SLT) users' exposure and response to SLT health warnings, which are currently in text-only format, covering 30% of the two primary surfaces of SLT containers and 20% of advertisements., Methods: Data were from the 2012-2013 National Adult Tobacco Survey. Past 30-day exposure to SLT health warnings among past 30-day SLT users (n=1626) was a self-report of seeing warnings on SLT packages: "Very often," "Often," or "Sometimes" (versus "Rarely" or "Never"). We measured the association between SLT health warning exposure and perceptions of SLT harmfulness and addictiveness using logistic regression., Results: Of past 30-day SLT users, 77.5% reported exposure to SLT health warnings, with lower prevalence reported among females and users of novel SLT products (snus/dissolvable tobacco). Furthermore, exposure reduced linearly with reducing education and annual household income (p<0.01). Among exposed past 30-day SLT users, 73.9% reported thinking about the health risks of SLT, while 17.1% reported stopping SLT use on ≥1 occasion within the past 30days. Exposure to SLT warnings was associated with perceived SLT harmfulness (AOR=2.16; 95% CI=1.15-4.04), but not with perceived SLT addictiveness., Conclusion: Socioeconomic disparities found in exposure and response to SLT health warnings can be addressed through implementation of large pictorial warnings., (Published by Elsevier Inc.)

Objective: Restricting tobacco marketing is a key element in the US Food and Drug Administration's (FDA) public health framework for regulating tobacco. Given the dearth of empirical data on direct marketing, the objective of this study was to assess the reach and impact of promotions on sales through snuff websites., Methods: Nine brands of snuff, representing more than 90% of market share, were monitored for content of coupons, sweepstakes, contests, and other promotions on their respective websites. Monthly sales data and website traffic for the 9 brands, corresponding to the 48-month period of January 2011 through December 2014, were obtained from proprietary sources. A time-series analysis, based on the autoregressive, integrated, moving average (ARIMA) method, was employed for testing the relationships among sales, website visits, and promotions., Results: Website traffic increased substantially during the promotion periods for most brands. Time-series analyses, however, revealed that promotion periods for 5 of 7 brands did not significantly correlate with monthly snuff sales., Conclusions: The success in attracting tobacco consumers to website promotions demonstrates the marketing reach of snuff manufacturers. This form of direct marketing should be monitored by the FDA given evidence of adolescents' exposure to cigarette brand websites.

Background: There is considerable interest from a regulatory and public health perspective in harmful and potentially harmful constituents in tobacco products, including smokeless tobacco products (STPs). A wide range of commercial STPs from the US and Sweden, representing 80-90 % of the 2010 market share for all the major STP categories in these two countries, were analysed for the IARC Group 2A carcinogen acrylamide. These STPs comprised the following styles: Swedish loose and portion snus, US snus, chewing tobacco, moist snuff, dry snuff, soft pellet, hard pellet and plug., Results: Acrylamide was detected in all the products tested and quantified in all but one product. Concentrations ranged from 62 to 666 ng/g wet weight basis (WWB). The average levels of acrylamide (WWB) by type of STP were not significantly different (p > 0.05) except for US snus which had, on average, greater levels but with a very wide range of individual levels according to the manufacturer. Acrylamide levels in STPs were significantly and positively correlated with pH, but not with levels of either reducing sugars or ammonia nitrogen. Levels of acrylamide increased by sixfold or more (on a dry weight basis) during manufacture of a snus sample and then decreased during subsequent storage for up to 22 weeks. Acrylamide generation in tobacco generally appears to occur at lower temperatures, but longer time scales than found with food production., Conclusions: Acrylamide is a common contaminant of STPs, formed through heat treatment of tobacco. Our data show that exposure to acrylamide from consumption of STPs is small compared with exposure from food consumption or cigarette smoking.

Super trajectory is reported of tobacco from his first meeting with the European man October 15, 1492. This plant was known in Europe by the publications of the Sevillan physician Nicolas Monardes (1574), the relations of friar Andrés Thevet (1575) and the famous botanical treatise of Charles de l'Écluse (1605). The Swedish botanist Karl Linnaeus inclused tobacco plant in the family Solanaceae and deleted from this group other plants that were intermixed with it. Its botanical name (Nicotiana tabacum) derived from the surname of the French ambassador to Portugal, Jean Nicot of Villemain, who in 1560 sent it to the Queen Mother of France Cathérine de Medicis. The use of snuff quickly spread throughout Europe, were it became common in the seventeenth century. By the late eighteenth century in New Spain, in addition to cigars, cigarettes and due in packs of different content the tobacco is concocted and price. The preparation of the different presentations of snuff, tobacco made in factories in the capital and several provincial cities, originated in 1796 the creation of the first kindergartens for the children of those working in them. This thanks to the successful initiative of then viceroy Marquis of Branciforte. But contrary to the forecasts of Father F. J. Clavijero and Mrs. F. Calderón de la Barca, wife of the first Spanish diplomatic representative to the government of Mexico, the use of tobacco, with the passage of time, far from waning has been increasing in every social class. And now, more than men, women are smokers., (Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.)

Background: Use of smokeless tobacco in the form of moist snuff placed in the oral cavity is popular in rural India. The aim of the present cross-sectional study was to determine the effect of snuff on periodontitis by assessing interleukin (IL)-1 β and IL-8 levels in gingival crevicular fluid., Materials and Methods: A total of 60 subjects were selected for this study. 40 subjects presented with periodontitis, which included 20 snuff users (SP) and 20 nonsnuff users (NS). 20 periodontally healthy patients formed the controls (healthy control: HC). The clinical parameters recorded were gingival index (GI), plaque index, calculus index, bleeding on probing (BOP), probing depth (PD), recession (RC), and clinical attachment level (CAL). The IL-1 β and IL-8 levels were assessed through enzyme-linked immunosorbent assay (Quantikine(®)). Analysis of variance (ANOVA), post-hoc Tukey's, Kruskal-Walli's ANOVA and Mann-Whitney test was used for comparison among groups and P > 0.05 was considered statistically significant., Results: No significant difference was seen in levels of IL-1 β and IL-8 between SP and NS groups (P = 0.16, 0.97). However, both the periodontitis groups (SP and NS) had increased IL-β levels when compared to HC group (P = 0.01, 0.001). The snuff users showed significant increase in GI, BOP, RC, and CAL when compared with NS (P = 0.002, 0.001, 0.012, 0.002) whereas NS group had significant increase in PD (P = 0.003)., Conclusion: Within the limitations of this study, use of snuff does not affect the host inflammatory response associated with periodontitis and leads to RC and increased CAL due to local irritant effect.

In this study, the association between physical activity and other potential determinants, objectively measured by accelerometry, was examined. Sixty-two men attending an infertility clinic participated in the study. Obese men (body mass index ≥ 30) and those with a waist circumference 102 cm or more had lower semen volume than the other men (P < 0.05). Higher values in sperm parameters were observed in participants who completed university studies and those who did not consume snuff, compared with the other participants (P < 0.05). Finally, men who spent an average number of 10 min-bouts of moderate-to-vigorous physical activity had significantly better semen quality than those who engaged in low or high numbers of bouts of activity (P < 0.05). No associations were found for sedentary or moderate-to-vigorous physical activity time when it was not sustained over 10 min, i.e. not in bouts. Men who have average levels of physical activity over sustained periods of 10 min are likely to have better semen quality than men who engage in low or high levels of such activity. Similarly, high levels of total and central adiposity, low educational level and snuff consumption are negatively related to semen quality., (Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: We assessed how varying definitions of adult current smokeless tobacco (SLT) use affected overall prevalence estimates., Methods: National prevalence estimates were from five surveys: 2009-2010 National Health and Nutrition Examination Survey (NHANES), 2009-2010 National Adult Tobacco Survey (NATS), 2010-2011 Tobacco Use Supplement of the Current Population Survey (TUS-CPS), 2010 National Survey on Drug Use and Health (NSDUH), and 2010 National Health Information Survey (NHIS). State-specific prevalence estimates were from three surveys: 2009-2010 NATS, 2010-2011 TUS-CPS, and 2010 Behavioral Risk Factor Surveillance System (BRFSS). Current SLT use definitions were as follows: past 5-day use (NHANES), past 30-day use (NATS and NSDUH), and "every day" or "some days" use (TUS-CPS, NHIS, and BRFSS). Inter-survey variations further existed in number and types of SLT products assessed., Results: National prevalence estimates of current SLT use were as follows: NATS (3.9%), NSDUH (3.6%), NHIS (2.8%), NHANES (2.3%), and TUS-CPS (1.6%). State-specific prevalence estimates of SLT use were generally lower for TUS-CPS (median=2.1%, range: 0.5% in California and New York, to 7.2% in Wyoming) compared to either BRFSS (median=4.0%: range: 0.9% in Washington D.C., to 8.2% in Wyoming) or NATS (median=4.7%; range: 1.3% in New Jersey, to 9.8% in Wyoming)., Conclusion: Concerted efforts are needed among interagency groups to harmonize SLT definition within different surveys., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Due to the lower health risks associated with the use of certain categories of smokeless tobacco products (STPs) such as Swedish snus, there is interest in the comparative levels of toxic chemical constituents in different types of STPs. A method has been developed and validated for the analysis of hydrazine in STPs. Seventy four commercial STPs from the US and Sweden, representing 80-90% of the 2010 market share for all the major STP categories in these two countries, as well as three reference STPs, were analysed for hydrazine., Results: Aqueous extracts of the STPs were treated with excess pentafluorobenzaldehyde (PFB), which reacted with hydrazine in solution to form decafluorobenzaldehyde azine (DFBA). DFBA was partitioned into hexane and then quantified by gas chromatography-mass spectrometry (GC-MS). The method was validated using five different types of STP, was linear in the range 8-170 ng/mL, and had limits of quantification (LOQ) from 26-53 ng of hydrazine per g of STP (as sold). The method was applied to the analysis of 74 contemporary STPs commercially available in the United States and Sweden, none of which were found to contain hydrazine above the LOQ or LOD. Trace levels of compounds showing chromatographic and mass spectral features consistent with hydrazine were identified at very low levels (sub-limit of detection, <10 ng/g) in the chromatograms of less than half of the 74 STPs examined; in contrast, for 40 of the STPs no evidence for the presence of hydrazine was observed. Where present, the levels of compounds consistent with hydrazine were estimated to be at least an order of magnitude lower than the only previous study to have quantified hydrazine in tobacco., Conclusions: Our results show that hydrazine is not a prevalent constituent of STPs, and when present is not quantifiable using currently available analytical methodology.

Although investigators have assessed the relationship between self-reported cigarette smoking and biomarker levels, the validity of self-reported information on smokeless tobacco (SLT) use is uncertain. We used aggregated data from the 2003-2004, 2005-2006, 2007-2008, and 2009-2010 administrations of the National Health and Nutrition Examination Survey (NHANES) to compare self-reported SLT use with serum concentrations of cotinine, a metabolite of nicotine, among US adults aged ≥18 years. Receiver operating characteristic analysis was used to determine the optimal serum cotinine cutpoint for discriminating SLT users from nonusers of tobacco, and concordance analysis was used to compare self-reported SLT use with cotinine levels. Among the 30,298 adult respondents who completed the NHANES during 2003-2010, 418 reported having exclusively used SLT and no other type of tobacco (cigarettes, cigars, or pipes) during the past 5 days, while 23,457 reported not using any tobacco. The optimal cotinine cutpoint for discriminating SLT users from non-tobacco users was 3.0 ng/mL (sensitivity=97.0%, specificity=93.0%), which was comparable to a revised cutpoint recommended for identifying adult cigarette smokers. Concordance with cotinine was 96.4% and 93.7% for self-reported SLT use and tobacco nonuse, respectively. These findings indicate that self-reported SLT use among adults correlates highly with serum cotinine levels and that the optimal cutpoint for minimizing misclassification of self-reported use is a serum cotinine concentration of 3.0 ng/mL., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Aim: This study examined the prevalence of tobacco habits and the influence of the social environment among Swedish female athletes representing both individual and team sports in Sweden., Material and Method: A self-reported cross-sectional survey was performed with 791 female athletes 15-24 years old representing ten of the most common sports in Sweden. The questions related to the participants' involvement in sports and their tobacco habits., Results: Findings revealed that a large proportion of the female athletes had never smoked (65%) or used snus (74%). However, a considerable portion of the participants had tried smoking (27%) or using snus (20%), especially those involved in team sports. Results also showed statistically significant associations between female athletes' smoking habits and those of both their mothers and their peers, but not with the tobacco habits of their coaches, indicating that coaches do not influence the female athletes' use of tobacco., Conclusion: In conclusion, this study indicated that the vast majority of female athletes did not use tobacco. A significant portion had sometimes tried tobacco, especially members of team sports, but this behaviour did not seem to be influenced by the tobacco habits of their coaches., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Statement of Problem: The increasing use of smokeless tobacco in the last 15 years has motivated researchers to evaluate its impact on its user's health., Purpose: The aim of this study was to determine the frequency of oral lesions related to smokeless tobacco and any possible correlation between the frequency of oral lesions and the amount of usage in patients referred to Zahedan Dental School., Materials and Method: A total of 90 (77 male and 13 female) cases, all snuff consumers, were surveyed in this cross sectional study which was accomplished by employing questionnaires. The questionnaire included demographic information, type and amount of smokeless tobacco used and the location where it was placed in the mouth. The completion of the questionnaires was followed by oral clinical examinations of patients. The location of any lesion found in soft tissue, was recorded in questionnaire., Results: The mean age for men and women was 47.7 and 55.61, respectively. A total of 38 cases (29 males, 9 females) were found to have oral lesions. 26 patients were using the snuff one pack per day. The common site of lesions was lower buccal sulcus. From 38 lesions, 32 lesions were found at the site of snuff placement. Most of the lesions were degree 1 and white in color. After taking biopsy from 32 lesions, 26 cases were detected as hyperkeratotic and 6 cases as epithelial dysplasia., Conclusion: This study showed that use of snuff is very common in Zahedan and usage of this material can produce oral lesions. There is not a significant correlation between the frequency of oral lesions and the amount of usage.

Background: Neutralizing antibodies (NAbs) to interferon β (IFNβ) products that develop during treatment are associated with a loss of clinical efficacy., Objectives: The aim of this study was to investigate the influence of smoking habits on the risk of developing NAbs to IFNβ, in the treatment of multiple sclerosis (MS)., Methods: This report is based on 695 MS patients treated with IFNβ-1a, included in two Swedish case-control studies that collected information on smoking habits. Using logistic regression, the development of NAbs to IFNβ-1a among current smokers was compared with that of non-smokers, by calculating the odds ratio (OR) with a 95% confidence interval (CI)., Results: Current smokers showed an increased risk of developing NAbs to IFNβ-1a, compared with non-smokers (OR 1.9; 95% CI 1.3-2.8; p = 0.002). There were no gender differences. We observed no association between past smoking and the risk of developing NAbs to IFNβ-1a., Conclusions: The finding that current smokers have an increased risk of developing NAbs to IFNβ-1a has implications, both for the practical care and the treatment of MS; it also provides an interesting perspective of the lungs as an immune-reactive organ, reacting upon irritation.